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Animal Models and Cell Lines

>Double Humanized Immune-Checkpoint Mice

Basic characteristics

 

Strain Name 

C57BL/6-Pdcd1tm1(hPDCD1)Lag3tm1(hLAG3)/Bcgen 

Common Name 

B-hPD-1/hLAG3 mice

Background 

C57BL/6 

Catalog number 

B-DM-005

Catalog number (Males) 

BDM005M 

Catalog number (Females) 

BDM005F

Related Genes


PD-1(Programmed death-1) ;

LAG3(Lymphocyte activation gene 3,CD223)


Targeting strategy

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Protein expression analysis 

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Fig 1. Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/hLAG3 mice were analyzed by flow cytometry. 

Mouse LAG3+ T cells were detected in both WT C57BL/6 and the homozygous B-hPD-1/hLAG3 mice, while human LAG3+ T cells were detected in the homozygous B-hPD-1/hLAG3 mice. This might result from the cross-recognition of hLAG3 by anti-mLAG3 antibodies.

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Fig 2. Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/hLAG3 mice were analyzed by flow cytometry. 

Mouse PD-1+ T cells were detected in the WT C57BL/6 mice, while human PD-1+ T cells were detected in the homozygous B-hPD-1/hLAG3 mice.


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Fig 3. Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/hLAG3 mice were analyzed by flow cytometry. 

Mouse PD-1+/LAG3+ T cells were detected in the WT C57BL/6 mice, while mouse LAG3+ T cells were detected in the homozygous B-hPD-1/hLAG3 mice, which might result from the cross-recognition of hLAG3 by anti-mLAG3 antibodies.

 

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Fig 4. Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/hLAG3 mice were analyzed by flow cytometry. 

Human PD-1+/LAG3+ T cells were detected in homozygous B-hPD-1/hLAG3 mice.


Combination therapy of PD-1(Keytruda) Ab and LAG3 Ab


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Fig 5. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hLAG3 mice.

Mice were grouped when the tumor size was approximately 150±50 mm3 (n=6). Anti-hLAG3 antibody shows no inhibitory effects, while the anti-hPD-1 antibody Keytruda shows modest tumor growth inhibition. On the other hand, combination of anti-hLAG3 antibody and the anti-hPD-1 antibody Keytruda shows more significant inhibition when compared to single Ab treatment. B-hPD-1 /hLAG3 mouse model is a powerful tool for in vivo efficacy evaluation of hPD-1 and hLAG3 antibody combination therapy. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.


 

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